Direct Keap1-kelch inhibitors as potential drug candidates for oxidative stress-orchestrated diseases: A review on In silico perspective

2021 ◽  
Vol 167 ◽  
pp. 105577
Author(s):  
Ibrahim Damilare Boyenle ◽  
Ukachi Chiamaka Divine ◽  
Rofiat Adeyemi ◽  
Kehinde Sulaimon Ayinde ◽  
Olamide Tosin Olaoba ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
In Silico ◽  
Potential Drug ◽  
Drug Candidates

scholarly journals Phytochemicals as potential drug candidates for targeting SARS CoV 2 proteins, an in silico study

VirusDisease ◽  
2021 ◽  
Author(s):  
Anish Nag ◽  
Ritesh Banerjee ◽  
Rajshree Roy Chowdhury ◽  
Chandana Krishnapura Venkatesh
Keyword(s):  
In Silico ◽  
Potential Drug ◽  
Drug Candidates ◽  
In Silico Study

scholarly journals In Vitro Assessment of the Neuroprotective and Antioxidant Properties of New Benzimidazole Derivatives as Potential Drug Candidates for the Treatment of Parkinson’s Disease

Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 54
Author(s):  
Anastassova ◽  
Argirova ◽  
Yancheva ◽  
Aluani ◽  
Tzankova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorders ◽  
Antioxidant Properties ◽  
Benzimidazole Derivatives ◽  
Potential Drug ◽  
Drug Candidates ◽  
In Vitro Assessment

Oxidative stress is related to the pathogenesis of many neurodegenerative disorders, including [...]

scholarly journals Viral Induced Oxidative and Inflammatory Response in Alzheimer’s Disease Pathogenesis with Identification of Potential Drug Candidates: A Systematic Review using Systems Biology Approach

2019 ◽  
Vol 17 (4) ◽  
pp. 352-365 ◽  
Author(s):  
Puneet Talwar ◽  
Renu Gupta ◽  
Suman Kushwaha ◽  
Rachna Agarwal ◽  
Luciano Saso ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Systems Biology ◽  
Candidate Genes ◽  
Protein Interactions ◽  
Interaction Network ◽  
Potential Drug ◽  
Human Herpes Virus 8 ◽  
Drug Candidates

Alzheimer’s disease (AD) is genetically complex with multifactorial etiology. Here, we aim to identify the potential viral pathogens leading to aberrant inflammatory and oxidative stress response in AD along with potential drug candidates using systems biology approach. We retrieved protein interactions of amyloid precursor protein (APP) and tau protein (MAPT) from NCBI and genes for oxidative stress from NetAge, for inflammation from NetAge and InnateDB databases. Genes implicated in aging were retrieved from GenAge database and two GEO expression datasets. These genes were individually used to create protein-protein interaction network using STRING database (score≥0.7). The interactions of candidate genes with known viruses were mapped using virhostnet v2.0 database. Drug molecules targeting candidate genes were retrieved using the Drug- Gene Interaction Database (DGIdb). Data mining resulted in 2095 APP, 116 MAPT, 214 oxidative stress, 1269 inflammatory genes. After STRING PPIN analysis, 404 APP, 109 MAPT, 204 oxidative stress and 1014 inflammation related high confidence proteins were identified. The overlap among all datasets yielded eight common markers (AKT1, GSK3B, APP, APOE, EGFR, PIN1, CASP8 and SNCA). These genes showed association with hepatitis C virus (HCV), Epstein– Barr virus (EBV), human herpes virus 8 and Human papillomavirus (HPV). Further, screening of drugs targeting candidate genes, and possessing anti-inflammatory property, antiviral activity along with a suggested role in AD pathophysiology yielded 12 potential drug candidates. Our study demonstrated the role of viral etiology in AD pathogenesis by elucidating interaction of oxidative stress and inflammation causing candidate genes with common viruses along with the identification of potential AD drug candidates.

scholarly journals Potential natural inhibitors of xanthine oxidase and HMG-CoA reductase in cholesterol regulation: in silico analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rishab Marahatha ◽  
Saroj Basnet ◽  
Bibek Raj Bhattarai ◽  
Prakriti Budhathoki ◽  
Babita Aryal ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Xanthine Oxidase ◽  
In Silico ◽  
Heart Diseases ◽  
Cholesterol Biosynthesis ◽  
Ligand Docking ◽  
In Vitro Assays ◽  
Potential Drug ◽  
Drug Candidates ◽  
Rate Limiting

Abstract Background Hypercholesterolemia has posed a serious threat of heart diseases and stroke worldwide. Xanthine oxidase (XO), the rate-limiting enzyme in uric acid biosynthesis, is regarded as the root of reactive oxygen species (ROS) that generate atherosclerosis and cholesterol crystals. β-Hydroxy β-methylglutaryl-coenzyme A reductase (HMGR) is a rate-limiting enzyme in cholesterol biosynthesis. Although some commercially available enzyme inhibiting drugs have effectively reduced cholesterol levels, most of them have failed to meet potential drug candidates’ requirements. Here, we have carried out an in-silico analysis of secondary metabolites that have already shown good inhibitory activity against XO and HMGR in a wet lab setup. Methods Out of 118 secondary metabolites reviewed, sixteen molecules inhibiting XO and HMGR were selected based on the IC50 values reported in in vitro assays. Further, receptor-based virtual screening was carried out against secondary metabolites using GOLD Protein-Ligand Docking Software, combined with subsequent post-docking, to study the binding affinities of ligands to the enzymes. In-silico ADMET analysis was carried out to explore their pharmacokinetic properties, followed by toxicity prediction through ProTox-II. Results The molecular docking of amentoflavone (GOLD score 70.54, ∆G calc. = − 10.4 Kcal/mol) and ganomycin I (GOLD score 59.61, ∆G calc. = − 6.8 Kcal/mol) displayed that the drug has effectively bound at the competitive site of XO and HMGR, respectively. Besides, 6-paradol and selgin could be potential drug candidates inhibiting XO. Likewise, n-octadecanyl-O-α-D-glucopyranosyl (6′ → 1″)-O-α-D-glucopyranoside could be potential drug candidates to maintain serum cholesterol. In-silico ADMET analysis has shown that these sixteen metabolites were optimal within the categorical range compared to commercially available XO and HMGR inhibitors, respectively. Toxicity analysis through ProTox-II revealed that 6-gingerol, ganoleucoin K, and ganoleucoin Z are toxic for human use. Conclusion This computational analysis supports earlier experimental evidence towards the inhibition of XO and HMGR by natural products. Further study is necessary to explore the clinical efficacy of these secondary molecules, which might be alternatives for the treatment of hypercholesterolemia.

scholarly journals In-Silico Analysis of Secondary Metabolites that Modulates Enzymes of Cholesterol Target

2020 ◽  
Author(s):  
Rishab Marahatha ◽  
Saroj Basnet ◽  
Bibek Raj Bhattarai ◽  
Prakriti Budhathoki ◽  
Babita Aryal ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
In Silico ◽  
Heart Diseases ◽  
Cholesterol Biosynthesis ◽  
In Silico Analysis ◽  
Ligand Docking ◽  
Potential Drug ◽  
Drug Candidates ◽  
Rate Limiting

AbstractHypercholesterolemia has posed a serious threat of heart diseases and stroke worldwide. Xanthine oxidase (XO), the rate-limiting enzyme in uric acid biosynthesis, is regarded as the root of reactive oxygen species (ROS) that generates atherosclerosis and cholesterol crystals. β-Hydroxy β-methylglutaryl-coenzyme A reductase (HMGR) is a rate-limiting enzyme in cholesterol biosynthesis. Although some commercially available enzyme inhibiting drugs have effectively reduced the cholesterol level, most of them have failed to meet the requirements of being apt drug candidates. Here, we have carried out an in-silico analysis of secondary metabolites that have already shown good inhibitory activity against XO and HMGR. Out of 118 secondary metabolites reviewed, sixteen molecules inhibiting XO and HMGR were taken based on IC50 values reported in vitro assays. Further, receptor-based virtual screening was carried out against secondary metabolites using GOLD Protein-Ligand Docking Software, combined with subsequent post-docking, to study the binding affinities of ligands to the enzymes. In-Silico ADMET analysis was carried out to study their pharmacokinetic properties, followed by toxicity prediction through ProTox-II. The molecular docking of amentoflavone (1) (GOLD score 70.54), and ganomycin I (9) (GOLD score 59.61) evinced that the drug has effectively bind at the competitive site of XO and HMGR, respectively. Besides, 6-paradol (3) and selgin (4) could be potential drug candidates to inhibit XO. Likewise, n-octadecanyl-O-α-D-glucopyranosyl(6’→1”)-O-α-D-glucopyranoside (10) could be potential drug candidates to maintain serum cholesterol. In-silico ADMET analysis showed that the sixteen metabolites were optimal within the categorical range in comparison to commercially available XO and HMGR inhibitors, respectively. Toxicity analysis through Protox-II revealed that 6-gingerol (2), ganoleucoin K (11), and ganoleucoin Z (12) are toxic for human use. This computational analysis supports earlier experimental evidence towards the inhibition of XO and HMGR by natural products. Further study is necessary to explore the clinical efficacy of these secondary molecules, which might be alternatives for the treatment of hypercholesterolemia.Graphical abstract

Recent Advances in the Development of Antimicrobial Peptides (AMPs): Attempts for Sustainable Medicine?

2018 ◽  
Vol 25 (21) ◽  
pp. 2503-2519 ◽  
Author(s):  
Anne Kokel ◽  
Marianna Torok
Keyword(s):  
Side Effects ◽  
Antimicrobial Peptides ◽  
Potential Drug ◽  
Green Technologies ◽  
Specific Antibodies ◽  
Structural Modifications ◽  
Drug Candidates ◽  
Induce Resistance ◽  
Conventional Antibiotics

Background: Since the first isolation of antimicrobial peptides (AMPs) they have attracted extensive interest in medicinal chemistry. However, only a few AMP-based drugs are currently available on the market. Despite their effectiveness, biodegradability, and versatile mode of action that is less likely to induce resistance compared to conventional antibiotics, AMPs suffer from major issues that need to be addressed to broaden their use. Notably, AMPs can lack selectivity leading to side effects and cytotoxicity, and also exhibit in vivo instability. Several strategies are being actively considered to overcome the limitations that restrain the success of AMPs. Methods: In the current work, recent strategies reported for improving AMPs in the context of drug design and delivery were surveyed, and also their possible impact on patients and the environment was assessed. Results: As a major advantage AMPs possess an easily tunable skeleton offering opportunities to improve their properties. Strategic structural modifications and the beneficial properties of cyclic or branched AMPs in term of stability have been reported. The conjugation of AMPs with nanoparticles has also been explored to increase their in vivo stability. Other techniques such as the coupling of AMPs with specific antibodies aim to increase the selectivity of the potential drug towards the target. These strategies were evaluated for their effect on the environment highlighting green technologies. Conclusion: Although further research is needed taking into account both environmental and human health consequences of novel AMPs, several of these compounds are promising drug candidates for use in sustainable medicine.

scholarly journals Canthin-6-one ameliorates TNBS-induced colitis in rats by modulating inflammation and oxidative stress. An in vivo and in silico approach

2021 ◽  
Vol 186 ◽  
pp. 114490
Author(s):  
Karuppusamy Arunachalam ◽  
Amilcar Sabino Damazo ◽  
Antonio Macho ◽  
Monica Steffi Matchado ◽  
Eduarda Pavan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
In Silico ◽  
And Oxidative Stress

10-gingerol induces oxidative stress through HTR1A in cumulus cells: in-vitro and in-silico studies

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Kiptiyah Kiptiyah ◽  
Widodo Widodo ◽  
Gatot Ciptadi ◽  
Aulanni’am Aulanni’Am ◽  
Mohammad A. Widodo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Culture ◽  
Superoxide Dismutase ◽  
In Silico ◽  
Cumulus Cell ◽  
Cumulus Cells ◽  
Sod Activity ◽  
In Silico Studies ◽  
Incubation Periods

AbstractBackgroundWe investigated whether 10-gingerol is able to induce oxidative stress in cumulus cells.MethodsFor the in-vitro research, we used a cumulus cell culture in M199, containing 10-gingerol in various concentrations (0, 12, 16, and 20 µM), and detected oxidative stress through superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentrations, with incubation periods of 24, 48, 72, and 96 h. The obtained results were confirmed by in-silico studies.ResultsThe in-vitro data revealed that SOD activity and MDA concentration increased with increasing incubation periods: SOD activity at 0 µM (1.39 ± 0.24i), 12 µM (16.42 ± 0.35ab), 16 µM (17.28 ± 0.55ab), 20 µM (17.81 ± 0.12a), with a contribution of 71.1%. MDA concentration at 0 µM (17.82 ± 1.39 l), 12 µM (72.99 ± 0.31c), 16 µM (79.77 ± 4.19b), 20 µM (85.07 ± 2.57a), with a contribution of 73.1%. Based on this, the in-silico data uncovered that 10˗gingerol induces oxidative stress in cumulus cells by inhibiting HTR1A functions and inactivating GSK3B and AKT˗1.Conclusions10-gingerol induces oxidative stress in cumulus cells through enhancing SOD activity and MDA concentration by inhibiting HTR1A functions and inactivating GSK3B and AKT˗1.

scholarly journals Apoptosis-like cell death upon kinetoplastid induction by compounds isolated from the brown algae Dictyota spiralis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Olfa Chiboub ◽  
Ines Sifaoui ◽  
Manef Abderrabba ◽  
Mondher Mejri ◽  
José J. Fernández ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Mitochondrial Membrane ◽  
Brown Seaweed ◽  
Cell Permeability ◽  
Oxygen Species ◽  
Potential Drug ◽  
Concentration Cell ◽  
Drug Candidates

Abstract Background The in vitro activity of the brown seaweed Dictyota spiralis against both Leishmania amazonensis and Trypanosoma cruzi was evaluated in a previous study. Processing by bio-guided fractionation resulted in the isolation of three active compounds, classified as diterpenes. In the present study, we performed several assays to detect clinical features associated to cell death in L. amazonensis and T. cruzi with the aim to elucidate the mechanism of action of these compounds on parasitic cells. Methods The aims of the experiments were to detect and evaluate specific events involved in apoptosis-like cell death in the kinetoplastid, including DNA condensation, accumulation of reactive oxygen species and changes in ATP concentration, cell permeability and mitochondrial membrane potential, respectively, in treated cells. Results The results demonstrated that the three isolated diterpenes could inhibit the tested parasites by inducing an apoptosis-like cell death. Conclusions These results encourage further investigation on the isolated compounds as potential drug candidates against both L. amazonensis and T. cruzi. Graphic abstract

Apigenin protects mice against 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced cholestasis

2021 ◽  
Vol 12 (5) ◽  
pp. 2323-2334
Author(s):  
Shihong Zheng ◽  
Peichang Cao ◽  
Zequn Yin ◽  
Xuerui Wang ◽  
Yuanli Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
Liver Fibrosis ◽  
Liver Damage ◽  
Liver Diseases ◽  
Potential Drug ◽  
Abnormal Lipid Metabolism ◽  
And Oxidative Stress

Apigenin prevented the DDC-induced abnormal lipid metabolism, liver damage and liver fibrosis by reducing inflammation and oxidative stress. Apigenin might be a potential drug for the treatment of cholestatic liver diseases.

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